Genome-wide profiling in colorectal cancer identifies PHF19 and TBC1D16 as oncogenic super enhancers

• Published in: Nature communications Vol. 12; no. 1; p. 6407
• Main Authors: Li, Qing-Lan, Lin, Xiang, Yu, Ya-Li, Chen, Lin, Hu, Qi-Xin, Chen, Meng, Cao, Nan, Zhao, Chen, Wang, Chen-Yu, Huang, Cheng-Wei, Li, Lian-Yun, Ye, Mei, Wu, Min
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 04-11-2021; Nature Publishing Group; Nature Portfolio
• Subjects: 38/15; 38/39; 38/88; 38/89; 45; 45/23; 45/77; 631/208/177; 631/208/514/1949; 631/67/68/2486; 631/67/69; 692/4028/67/1504/1885; Animals; Cancer; Cell Line; Chromatin Immunoprecipitation Sequencing; Circuits; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - genetics; Enhancers; Epigenetics; Epigenomics; Gene Expression Profiling; Gene Expression Regulation, Neoplastic - genetics; Gene Expression Regulation, Neoplastic - physiology; Gene sequencing; Genomes; Genomics; Humanities and Social Sciences; Humans; Loci; Male; Mice; Mice, Inbred BALB C; multidisciplinary; Mutation; Nucleotides; Science; Science (multidisciplinary); Sequence Analysis, RNA; Single-nucleotide polymorphism; Tissues; Transcription factors; Tumorigenesis; Whole genome sequencing
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-26600-5

Colorectal cancer is one of the most common cancers in the world. Although genomic mutations and single nucleotide polymorphisms have been extensively studied, the epigenomic status in colorectal cancer patient tissues remains elusive. Here, together with genomic and transcriptomic analysis, we use ChIP-Seq to profile active enhancers at the genome wide level in colorectal cancer paired patient tissues (tumor and adjacent tissues from the same patients). In total, we sequence 73 pairs of colorectal cancer tissues and generate 147 H3K27ac ChIP-Seq, 144 RNA-Seq, 147 whole genome sequencing and 86 H3K4me3 ChIP-Seq samples. Our analysis identifies 5590 gain and 1100 lost variant enhancer loci in colorectal cancer, and 334 gain and 121 lost variant super enhancer loci. Multiple key transcription factors in colorectal cancer are predicted with motif analysis and core regulatory circuitry analysis. Further experiments verify the function of the super enhancers governing
PHF19
and
TBC1D16
in regulating colorectal cancer tumorigenesis, and KLF3 is identified as an oncogenic transcription factor in colorectal cancer. Taken together, our work provides an important epigenomic resource and functional factors for epigenetic studies in colorectal cancer.
Active enhancers are still understudied in colorectal cancers (CRC). Here the authors analyse active enhancers in CRC patients using genomics, transcriptomics, and epigenomics, identifying and validating variant super-enhancer loci as well as KLF3 as a relevant transcription factor.